When a protein is introduced into the blood stream of an animal, including humans, to which that protein is foreign, the protein acts as an antigen and elicits an immunological response which results in a cell mediated response and in the production of antibodies of the immune system of the animal. Such antibodies are specific to the particular injected antigen in the sense that a given antibody will bind in a complex as an immune reaction, i.e., undergo complexation, only with the specific antigen by which it was generated but may also produce cross-reactions between an antibody and antigens closely related to that for which such antibody is specific.
When an animal is invaded by a disease-producing organism which enters its system, the invading organism acts as an antigen and thus eventually evokes an immune response thereto. However, if the animal has never previously been exposed to the particular invading organism, its system has had no opportunity to produce antibodies to that organism so that the immunological response of the animal may be slow to develop and before such development has taken place, the attack of the organism may have become so invasive or massive as to cause a prolonged illness or even death if the animal's immunological defenses are sufficiently overwhelmed.
In order to convey an immunity in advance to the attack of serious disease-producing organisms, vaccines have been developed which are traditionally administered for prophylatic purposes, i.e., to expose the animal to a specific invading disease-producing antigen in such limited quantities or in such an inactivated or weakened condition that the immunological system of the body can safely develop an adequate supply of antibodies for the pathological antigen as to confer protection against subsequent exposures to that antigen but without seriously risking an invasive attack by the administered antigen, although unfortunately such attacks can occur in rare instances with, for example, hypersensitive individuals.
Obviously, since the prophylactic approach can rarely be totally implemented throughout an entire population, it is desirable to have available to the physician therapeutic resources that can be administered to patients already suffering with a given disease. The fact that the disease is already in progress in a patient naturally denotes that the immunological defenses of that patient were insufficient to withstand the invasion of the disease, and reinforcement or stimulation of the thus inadequate immunological defenses can be achieved in two ways. First, a serum or antitoxin can be derived from the blood of another individual who was previously exposed to the particular disease, either naturally or by prophylactic vaccination, and which serum, therefore, already contains antibodies against the specific disease. Various serums have been developed and can be administered to patients suffering from the disease for treatment of same, the antibodies provided by the serum aiding in neutralizing the noxious antigen until the time the patient's own immunological system has become enhanced and is capable of combatting the disease.
Alternatively, in certain instances, therapeutic vaccines have been developed which contain the specific antigen corresponding to the on-going disease to be treated for purposes of therapeutic administration to evoke a stronger immunological reaction for assisting in overcoming the further course of the disease. Generally, such a therapeutic antigenic vaccine is useful for diseases which have an extended incubation period, i.e., a considerable time lapse between time of exposure and actual symptomatic manifestation of the disease in the patient, such as rabies. Obviously, if the disease is already well established, then the introduction of added antigens of the same type is normally contraindicated, serving only to aggravate the existing imbalance between the invading organisms and the already strained immunological defenses of the patient. However, if the onset of the disease is delayed following a recognized exposure, then injection of the same antigen in altered, e.g., weakened form, can serve in the interim to provoke the immunological system to produce antibodies thereagainst which will then be present to combat the development of the disease at the end of its incubation period.
Antigenic vaccines are also administered for diagnostic purposes, i.e., to provide a perceptible indication of whether or not a given individual has been previously exposed to a disease-producing organism and thus already contains antibodies for that organism in its system. An example is the tuberculin vaccine employed to signify the presence or not of antibodies for the tuberculin bacillus.
Typically, where therapeutic antigenic vaccines have been employed, such employment has been specific to the precise antigenic disease-producing organism that is to be combatted or detected as the case may be. Given the known specificity of the antigen-antibody response, it follows that the same antigen needs to be selected for therapeutic intervention for the corresponding disease. For example, if introduction of say a tetanus bacteria into the system is suspected, the physician administers a tetanus vaccine and not a rabies vaccine or a tuberculin vaccine. However, in recent years a non-specific response to antigenic administration has received limited recognition. Thus, it has been proposed to administer a bacille Calmette Guerin (BCG) (see Barber, "Immunobiology for the Clinician", J. Wiley & Sons, 1977, pp. 239, 240) vaccine for the treatment of malignant tumors, particularly in combination with other anti-tumor therapy with some success. BCG has also been proposed in U.S. Pat. No. 3,849,551 as an adjuvant in a non-living malaria vaccine. Such "adjuvants" are considered to lack immunological activity in themselves, but to enhance or promote the immunological response elicited from certain other antigenic materials. Other examples of adjuvants are the so-called Freunds adjuvant, complete and incomplete, which consists of a water-in-oil emulsion containing a suspension of killed tubercle bacilli, as well as mycobacteria other than BCG as disclosed in U.S Pat. No. 3,876,779.
A polyvalent vaccine described as having the capacity to stimulate non-specifically the immune systems of a patient to which it is administered is described in U.S. Pat. No. 4,341,762 to Haast. This vaccine is constituted of a mixture of plural snake venom components: a first component acting as a post-synaptic neurotoxin, derived from "cobra" venom, a second component having a pre-synaptic neurotoxin activity derived from "krait" venom and a third component derived from "viper" venom to which is primarily attributed immuno-stimulating capability, although the other two components are also said to have some immuno-stimulatory effect. This vaccine is said to be useful for the treatment of progressive degenerative neurological diseases such as multiple sclerosis, muscular distrophy and Parkinson's disease, and diseases of known or potential viral origin, such as the herpes complex, and for mitigating autoimmune disorders, such as the arthritis complex, as well as diabetes. The venom components of the Haast vaccine, while not subjected to a chemical detoxification treatment, as characterized an earlier vaccine for neurological disorders described in U.S. Pat. Nos. 3,888,977 and 4,126,676 to Sanders, were rendered safe for human administration by means of individual complex purification and extractive procedures to remove noxious or toxic constituents therefrom, while preserving the bioactivity of the desirable active fractions thereof.